Defective expression and function of the leukocyte associated ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients

Barbara M. Colombo, Paolo Canevali, Ottavia Magnani, Edoardo Rossi, Francesco Puppo, Maria Raffaella Zocchi, Alessandro Poggi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20 + B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.

Original languageEnglish
Article numbere31903
JournalPLoS One
Volume7
Issue number2
DOIs
Publication statusPublished - Feb 15 2012

Fingerprint

lupus erythematosus
Lymphocytes
Systemic Lupus Erythematosus
B-lymphocytes
leukocytes
Leukocytes
B-Lymphocytes
Collagen
Immunoglobulins
receptors
collagen
NF-kappa B
Cells
immunoglobulins
Mixed Connective Tissue Disease
Chemical activation
transcription factor NF-kappa B
Tissue
rheumatoid arthritis
stromal cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Defective expression and function of the leukocyte associated ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients. / Colombo, Barbara M.; Canevali, Paolo; Magnani, Ottavia; Rossi, Edoardo; Puppo, Francesco; Zocchi, Maria Raffaella; Poggi, Alessandro.

In: PLoS One, Vol. 7, No. 2, e31903, 15.02.2012.

Research output: Contribution to journalArticle

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